Immunostimulatory Single-Stranded Ribonucleic Acid with Phosphodiester Backbone
AssigneeColey Pharmaceutical GmbH
InventorStefan Bauer
Life of this patent
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Abstract
Immunostimulatory single-stranded oligoribonucleotides (ssORN) with phosphodiester backbones induce TLR7-independent and MyD88-dependent immune activation. These immunostimulatory ssORN are useful to induce a ThI-like immune response in a subject, to induce an antigen-specific immune response in a subject, and to treat a subject having a cancer, an infectious disease, an allergic condition, or asthma.
Claims12
A method of inducing a Th1-like immune response in a subject, the method comprising
- administering to the subject an effective amount of an immunostimulatory single-stranded oligoribonucleotide (ssORN) 5-100 nucleotides long, wherein the immunostimulatory ssORN has a phosphodiester backbone and comprises a nucleotide sequence that
- (1) is free of guanosine (G), or
- (2) comprises at least one G, with proviso that when the nucleotide sequence comprises at least one G, the nucleotide sequence is
- (a) free of uridine (U), and
- (b) free of CpG motif X1X2CGX3X4, wherein X1, X2, X3, and X4 are nucleotides and CG is a cytosine (C)-guanine (G) dinucleotide, wherein the C of the CG dinucleotide is unmethylated,
- with proviso that the immunostimulatory ssORN is not present as part of a double-stranded ribonucleic acid (RNA) molecule.
A method of inducing an antigen-specific response in a subject, the method comprising
- administering to the subject an antigen;
- and
- administering to the subject an effective amount of an immunostimulatory single-stranded oligoribonucleotide (ssORN) 5-100 nucleotides long, wherein the immunostimulatory ssORN has a phosphodiester backbone and comprises a nucleotide sequence that
- (1) is free of guanosine (G), or
- (2) comprises at least one G, with proviso that when the nucleotide sequence comprises at least one G, the nucleotide sequence is
- (a) free of uridine (U), and
- (b) free of CpG motif X1X2CGX3X4, wherein X1, X2, X3, and X4 are nucleotides and CG is a cytosine (C)-guanine (G) dinucleotide, wherein the C of the CG dinucleotide is unmethylated,
- with proviso that the immunostimulatory ssORN is not present as part of a double-stranded ribonucleic acid (RNA) molecule.
A method of treating a subject having a cancer, the method comprising
- administering to the subject an effective amount of an immunostimulatory single-stranded oligoribonucleotide (ssORN) 5-100 nucleotides long, wherein the immunostimulatory ssORN has a phosphodiester backbone and comprises a nucleotide sequence that
- (1) is free of guanosine (G), or
- (2) comprises at least one G, with proviso that when the nucleotide sequence comprises at least one G, the nucleotide sequence is
- (a) free of uridine (U), and
- (b) free of CpG motif X1X2CGX3X4, wherein X1, X2, X3, and X4 are nucleotides and CG is a cytosine (C)-guanine (G) dinucleotide, wherein the C of the CG dinucleotide is unmethylated,
- with proviso that the immunostimulatory ssORN is not present as part of a double-stranded ribonucleic acid (RNA) molecule.
A method of treating a subject having an infectious disease, the method comprising
- administering to the subject an effective amount of an immunostimulatory single-stranded oligoribonucleotide (ssORN) 5-100 nucleotides long, wherein the immunostimulatory ssORN has a phosphodiester backbone and comprises a nucleotide sequence that
- (1) is free of guanosine (G), or
- (2) comprises at least one G, with proviso that when the nucleotide sequence comprises at least one G, the nucleotide sequence is
- (a) free of uridine (U), and
- (b) free of CpG motif X1X2CGX3X4, wherein X1, X2, X3, and X4 are nucleotides and CG is a cytosine (C)-guanine (G) dinucleotide, wherein the C of the CG dinucleotide is unmethylated,
- with proviso that the immunostimulatory ssORN is not present as part of a double-stranded ribonucleic acid (RNA) molecule.
A method of treating a subject having an allergic condition, the method comprising
- administering to the subject an effective amount of an immunostimulatory single-stranded oligoribonucleotide (ssORN) 5-100 nucleotides long, wherein the immunostimulatory ssORN has a phosphodiester backbone and comprises a nucleotide sequence that
- (1) is free of guanosine (G), or
- (2) comprises at least one G, with proviso that when the nucleotide sequence comprises at least one G, the nucleotide sequence is
- (a) free of uridine (U), and
- (b) free of CpG motif X1X2CGX3X4, wherein X1, X2, X3, and X4 are nucleotides and CG is a cytosine (C)-guanine (G) dinucleotide, wherein the C of the CG dinucleotide is unmethylated,
- with proviso that the immunostimulatory ssORN is not present as part of a double-stranded ribonucleic acid (RNA) molecule.
A method of treating a subject having asthma, the method comprising
- administering to the subject an effective amount of an immunostimulatory single-stranded oligoribonucleotide (ssORN) 5-100 nucleotides long, wherein the immunostimulatory ssORN has a phosphodiester backbone and comprises a nucleotide sequence that
- (1) is free of guanosine (G), or
- (2) comprises at least one G, with proviso that when the nucleotide sequence comprises at least one G, the nucleotide sequence is
- (a) free of uridine (U), and
- (b) free of CpG motif X1X2CGX3X4, wherein X1, X2, X3, and X4 are nucleotides and CG is a cytosine (C)-guanine (G) dinucleotide, wherein the C of the CG dinucleotide is unmethylated,
- with proviso that the immunostimulatory ssORN is not present as part of a double-stranded ribonucleic acid (RNA) molecule.
Dependencies are inferred from the claim text.